Effects of H1 and H2 histamine receptor antagonists on positive feed-back effect of estrogen on LH in prepubertal female rats.

The aim of the present study was to determine whether histaminergic central mechanisms which exert a well known effect on gonadotrophin secretion are involved in the development of the positive feed-back effect of estrogen-progesterone (E-P) on LH secretion that normally occurs in female rats about 20-22 days old. The administration of histamine H2 (cimetidine and ranitidine) or H1 (diphenhydramine) receptor blocking agents did not modify the onset of the LH release response to E-P. Nevertheless cimetidine, ranitidine and diphenhydramine potentiated the LH release induced by ovarian steroids at 23 days of age. These results appear to indicate that histaminergic pathways are involved in the magnitude of the LH response to E-P in prepubertal female rats rather than in the maturation of this mechanism.

Effect of naloxone on the development of the positive feed-back action of oestrogen-progesterone on LH secretion in rats.

The purpose of this study was to examine the role of opiate peptides in the development of the positive feedback effect of ovarian hormones (Oe-P) on the LH secretion that matures in female rats at about the age of 20-22 days. Oe-P administration at the age of 14 days induced a significant decrease of LH levels. A single injection of naloxone (5 mg/kg) induced a significant release of LH. This release was completely blocked by Oe-P administration. At the age of 20 days, Oe-P did not induce any significant change of LH levels, whereas naloxone increased the serum LH concentration. On the other hand, injection of Oe-P into naloxone-treated rats induced a significant rise in LH that was significantly higher than that observed with naloxone alone (P less than 0.025). Oe-P administration induced a positive feedback effect on LH at the age of 25 days. At this age, naloxone also increased LH levels and a significant potentiation of the LH release in response to Oe-P was observed in a group treated with naloxone. These results indicate that naloxone advances the development of the positive feedback mechanism of ovarian hormones on LH secretion and potentiates this mechanism after its maturation. On this basis it is proposed that the probable inhibitory effect of opiates on the onset of the positive feedback mechanism is related to the well-known participation of the opiate system in the onset of puberty.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of sexual differentiation of the hypothalamus in the differential effect of the serotoninergic system on LH in prepubertal male and female rats.

5-hydroxytryptophan (5-HTP), a serotonin precursor, has been shown to induce LH release in female but not in male rats at 16, 18 and 20 days of age. The purpose of this study was to investigate the role of neonatal gonadal hormones on 5-HTP-induced LH release in male and female rats of 16 and 20 days of age. The following groups of rats were studied control females, androgenized females, control males, and castrated males. Androgenization and castration were performed within 48 h of birth. 5-HTP administration increased LH concentration in normal females and castrated males at 16 and 20 days of age. The LH release response to 5-HTP was significantly lower at 20 than at 16 days of age in both groups. Neonatal androgenization abolished the LH release response in prepubertal female rats. These results indicate that neonatal exposure to androgen is responsible for the sex difference in the LH response to 5-HTP, which may be associated with a regulatory action of serotonin on the cyclic hypothalamic control of gonadotrophin secretion.

Sexual differences in the effect of serotonin on LH secretion in rats.

The effect of 5-hydroxytryptophan (5-HTP), a serotonin (5-HT) precursor, on luteinizing hormone (LH) secretion was studied in prepubertal male and female rats of different ages. In females 5-HTP stimulated LH release on days 16, 18 and 20 but not in older rats (26, 30, 35 days of age). No effects of 5-HTP on LH levels were observed in males. The positive feed-back mechanism of oestrogen-progesterone (E-P), that normally matures in the female between 20 and 26 days, was inhibited by 5-HTP in all the ages studied during prepuberty (26, 30 and 35 days old). On the other hand, in adult ovariectomized rats, 5-HTP administration not only decreased the high LH levels induced by ovariectomy, but the LH release response to E-P as well. These results indicate that there are sexual differences in the effect of 5-HT on LH in prepubertal rats younger than 26 days old. Administration of p-chloroamphetamine (PCA) a serotonin neurotoxin selective for serotoninergic neurons that depletes 5-HT levels in the brain, induced a significant increase in the LH release response to LRH in females, but had no effect in males. These results, besides suggesting a probable pituitary participation in the 5-HT action on LH secretion in the female, appear to indicate the existence of sexual differences in the effect of 5-HT in adult rats.

Effect of the serotoninergic system on luteinizing hormone secretion in prepubertal female rats.

The effect of 5-hydroxytryptophan (5-HTP), a serotonin precursor, and p-chloroamphetamine (PCA), a serotonin neurotoxin, selective for serotoninergic neurons, that depletes serotonin (5-HT) levels in brain, on the luteinizing hormone (LH) release response to estrogen-progesterone (E-P) was studied in prepubertal female rats of different ages. E-P decreased LH levels on days 16, 18 and 20, increasing the levels of the pituitary hormone at day 26 of age. Destruction of the serotoninergic system advanced the onset of the positive feed-back mechanism, since the rats pretreated with PCA showed at day 20 an LH release by E-P administration while in the controls of the same age the ovarian hormones decreased the LH concentration. On the other hand, PCA potentiated the positive feed-back mechanism of E-P on LH in 26-day-old rats, while at this age the LH release response to E-P was significantly reduced by the administration of 5-HTP. These results suggest that the serotoninergic system has an inhibitory effect on the development of the positive feed-back of ovarian steroids on LH secretion, that could be representative of a regulatory participation of serotonin in the onset of puberty. 5-HTP stimulated LH release on days 16, 18 and 20, but did not modify the LH concentration of day 26. Since between 20 and 26 days of age the positive feed-back mechanism matures, the possibility arise that the modification in the effect of serotonin on LH release on day 26 is connected with the physiological changes in the gonadotropin control that occur after day 20 in the female rat.

Pinealectomy advances the time of development of steroid feedback on luteinizing hormone release in immature female rats.

The effect of pinealectomy (Px) on the development of steroid positive feedback on luteinizing hormone (LH) release was examined in female rats subjected to surgery at 10 days of age. Estradiol-progesterone injection decreased serum LH in sham Px or intact controls younger than 20 days, while a significant LH release was found at day 22; Px rats showed a steroid-induced LH depression only at day 16, a positive feedback being detectable at day 20, 2 days earlier than in sham Px or intact rats. Daily injections of 10-50 micrograms melatonin to intact rats disrupted the LH negative feedback response at day 20, and diminished steroid-induced LH release at day 24.

Failure of melatonin to increase serum prolactin levels in ovariectomized rats subjected to superior cervical ganglionectomy or pinelaectomy.

The effects of melatonin on serum prolactin levels were examined in ovariectomized rats primed with oestradiol and progesterone, and subjected to bilateral superior cervical ganglionectomy or pinealectomy. Ganglionectomy resulted in a significant depression of the serum prolactin concentrations, as well as in impairment of the prolactin release evoked by administration of steroid. Treatment with melatonin increased serum prolactin in control but not in ganglionectomized rats. Injection of melatonin protentiated the steroid-induced release of prolactin in control rats; this effect of melatonin was not detected in ganglionectomized rats. Pinealectomy did not affect basal prolactin levels, nor impair the release of prolactin evoked by steroid treatment; however, it was effective in blocking the melatonin-induced release of prolactin in vehicle-treated rats, as well as the potentiation of steroid-induced prolactin release by melatonin. Intracranial surgery by itself increased prolactin release. These results suggest that systemically administered melatonin needs an intact pineal gland to augment serum prolactin levels.

Effect of melatonin and superior cervical ganglioectomy on luteinizing hormone on release induced by estradiol-progesterone in castrated rats.

The effect of melatonin on luteinizing hormone (LH) relase was studied in castrated female rats injected with estradiol and progesterone. Melatonin administered s.c. twice daily for 6 days exerted a biphasic, dose-related effect on LH release, the lowest dose (125 micrograms/100 g body weight) being stimulatory and the highest (250 micrograms/100 g body weight) inhibitory. Superior cervical ganglionectomy negated the inhibitory effect of the high metatonin dose on steroid-induced LH release. Rather melatonin injection to ganglionectomized rats resulted in significantly higher serum LH values than those of animals injected with estradiol and progesterone alone. Melatonin treatment failed to modify postcastration serum LH levels.

Effect of estradiol on aminoacid incorporation into proteins of different hypothalamic areas in prepuberal rats.

Estradiol in vitro produces a significant increase in the incorporation of 3H-leucine into proteins of the anterior hypothalamic area in prepuberal female rats, 15 and 20 days old, but not in younger animals. The ovarian hormone induced no changes in the protein synthetic activity of middle and posterior hypothalamus and cerebral cortex in prepuberal female rats of different ages. Estradiol did not modify the protein synthesis of the hypothalamus and cerebral cortex in prepuberal male rats.

Effect of castration upon hypothalamic luteinizing hormone releasing factor (LH-RF).

The effect of castration upon hypothalamic LH-RF synthesis and content was determined in mature male rats. In each single experiment 20 hypothalami from both normal and 60-day-castrated rats were bisected into symmetrical portions. For the determination of LH-RF synthesis 20 hypothalamic halves were incubated for 120 min. After incubation the tissue was homogenized in medium containing 1 N acetic acid, and centrifuged; 1.0 ml of the supernatant was used to test LH-RF activity. In the other 20 halves, hypothalamic LH-RF content was determined: the samples were homogenized without incubation in 1 N acetic acid, centrifuged, and LH-RF activity was tested in 1.0 ml of the supernatant. LH-RF activity was determined in vivo in ovariectomized rats pre-treated with estrogen-progesterone by measuring, by radioimmunoassay, the LH modifications in serum after the i.v. administration of the extracts. Hypothalamic LH-RF content was significantly higher in control than in castrated rats (p is less than 0.001). After incubation there were no changes in the LH-releasing potency of control hypothalami compared with non-incubated tissue, whereas a significant increase (616%) was found after the incubation of hypothalami from castrated rats. On the other hand, after incubation LH-RF activity was higher (p is less than 0.02) in castrated than in control hypothalami. These results suggest that castration stimulates the release and synthesis of hypothalamic LH-RF in male rats.